Background: The selection of the correct donor lung is crucial for a successful lung transplant. Since the median survival after lung transplant is 5 years and the morbidity and mortality of lung transplant is higher than other transplants, it is crucial to preselect the correct recipient. Methodology: In India, Dr. P. Venugopal at the All India Institute of Medical Sciences, New Delhi, performed the first successful heart transplant, while Dr. K. M. Cherian performed the first heart–lung transplant at Chennai. At Apollo Hopsitals, Chennai, the first heart transplant was performed by Dr. M. R. Girinath. Subsequently, the Department of Heart and Lung Transplantation at Apollo Hospitals, Chennai, have performed a large number of heart and lung transplants and its experience is summarized. Results: The Department of Heart and Lung Transplantation at Apollo Hospitals, Chennai, has done 101 lung and 62 heart transplants as part of their lung and heart lung transplant program. There were 21 heart–lung transplants and 25 double lung transplants. The results are discussed and indications, contraindications for lung and heart–lung transplant as well as recipient and donor workup are discussed in this first part of a set of three articles. Conclusions: Careful selection of a recipient and donor leads to a successful lung and heart–lung transplant program.

Lung transplantation in humans was first attempted almost 55 years ago by James Hardy in 1963.[1] There were a lot of problems in the initial decades because of rejection and anastomotic site healing. Rejection rates improved with the introduction of cyclosporin. Improved surgical techniques were also devised.

There were no long-term survivors for two decades. About 44 patients worldwide underwent lung transplant with no long-term survivors.[2] It was only in 1983 that Joel Cooper reported the first successful single lung transplant in humans.[3] Gradually, with better surgical techniques and better understanding of the lung transplant physiology and immunology, the results improved and now the survival is 80% at 1 year, 65% at 3 years, and 54% at 5 years [Figure 1].

In India, the first successful heart transplant was performed at All India Institute of Medical Sciences by Dr. P. Venugopal [Figure 2] in 1994.[4] The first successful heart–lung transplant in India was performed by Dr. KM Cherian [Figure 3] at Chennai.[5] At Apollo Hospitals, Chennai, the first heart transplant was performed by Dr. M. R. Girinath [Figure 4] in 1995. At that time, there was no formal transplant program and sporadic cases were performed in the next 2 years with varying results and subsequently, no further heart transplants were done. A formal Cardiothoracic Transplant program at Apollo Hospitals, Chennai, was envisioned by the transplant team of Dr. Paul Ramesh and Dr. T. Sunder, cardiothoracic surgeons and their first step was to develop a multidisciplinary team of specialists who were passionate about transplant and the department was built and protocols developed – largely from the Papworth Hospitals in the UK. The transplant program was largely a surgeon-led program. The first heart transplant successfully done by this group was in 2006. Over the years, problems specific to the Indian scenario were encountered and protocols were tailored to meet Indian conditions.

Figure 2: Dr. P.Venugopal who performed first heart transplant in India.

The first heart–lung transplant at Apollo Hospitals, Chennai, and second in India was performed by Dr. Paul Ramesh and Dr. T. Sunder in 2007. With the experience gained in dealing with heart transplants in Indian patients, both recipients and donors, the team commenced the lung transplant program. In 2011, the transplant team grew with addition of Dr. Madhan Kumar – also a cardiothoracic surgeon. In 2016, Dr. Suresh Manickavel, transplant physician and pulmonologist joined the Apollo Heart and Lung Transplant team [Figure 5]. At Apollo Hospitals, Chennai, the first isolated lung transplant was performed in 2011 by Dr. Paul Ramesh, Dr. Madhan Kumar, and Dr. T. Sunder, which was a single lung transplant. The unit has then progressed to performing double lung transplants and preferentially performs double lung transplants whenever possible.

Live-related Kidney transplants were performed since 1983 when the Hospital started functioning under the stewardship of Dr. Mani. After the passing of the Transplantation of Human Organs Act in 1994, cadaveric-deceased donor kidney transplants are being regularly done.

Some of the problems faced by the lung transplant units in India[5] include late referral, reluctance of physicians to refer cases due to lack of confidence in surgical outcomes, bed bound and sick patients who have developed myopathies and are therefore not very good surgical patients, ventilator dependence of patients, ventilator-associated pneumonia and graft dehiscence, and tubercular infection both in the recipient and the donor.

Selection of the lung for lung transplant and the correct recipient is crucial for a successful lung transplant. The indications for lung transplant have been detailed by the pulmonary transplantation council of the International Society for Heart and Lung Transplant 2014. Referral for lung transplant should occur early in end-stage lung disease, but the guidelines for India need to be evolved with experience and time. This document will try to document the experience of one hospital as a model and then try to document the experiences of other hospitals similarly to evolve a consensus.

Methodology

The AIIMS and Apollo Hospital Chennai are organizing a series of 3 hands on workshops on heart–lung transplant [Figure 6]. The proceedings will be published in this journal and will act as a starting point for hospitals who want to start their own transplant programs.

Figure 6: Participants of the lung transplant workshop at AIIMS, New Delhi.

The selection process for the donor and recipient is highlighted in this document and the Indian experience for each component is expanded by the Apollo experience.

Results

The Heart and Lung Transplant Team, Apollo Hospitals, Chennai, has assessed a total of about 154 patients and transplanted 163 organs in 94 patients. This includes 101 lungs and 62 hearts. There were 39 heart transplants with three bridge to transplants where two were bridged from a ventricular-assist device and one from an extracorporeal membrane oxygenator. There were 21 combined heart and lung transplants. There was one combined heart–lung and kidney transplant. There was one combined heart and liver transplant, which was an en bloc heart–liver transplant, the first of its kind in Asia. There were 25 double lung transplants including one bridged from an extracorporeal membrane oxygenator. There were seven single lung transplants including one being bridged from a ventilator. Postsurgery, 89.3% of the heart transplant patients were doing well and 73% of the lung transplant patients were doing well (80% survival in primary pulmonary hypertension and 67% survival in interstitial lung disease [ILD]) [Figure 7] and [Figure 8].

Figure 8: Apollo Heart and Lung Transplant Team with the oldest recipient of heart-lung transplant in India after an uneventful laparoscopic cholecystectomy 4 years post transplant under general anaesthesia

Heart–lung and lung transplant in India is in its infancy with limited centers doing the procedure. We have presented the experience of the Department of Heart and Lung Transplantation, Apollo Hospitals, Chennai, which has one among the largest numbers of lung transplants in India and has discussed the selection process for the recipient and the donor.

Recipient aspects

Indications for lung transplant

This section deals with indications for lung transplant,[6],[7] both general aspects and objective criteria that need to be met in different groups of lung disease (disease-specific indications).

>80% chance of surviving 5 years from a medical perspective, provided the graft (transplanted lung) function is adequate.

Disease-specific indications

These include specific objective criteria, in different lung diseases, which need to be present in order to consider lung transplantation.[8]

Interstitial lung disease

Patients are referred when there is interstitial pneumonitis or fibrosing nonspecific interstitial pneumonitis[8] with forced vital capacity <80% predicted, diffusing capacity of the lung for carbon monoxide <40% predicted, and desaturation to <88% on room air [Table 2].

Treatment for pulmonary artery hypertension is largely medical with pulmonary vasodilators and transplantation is only indicated[8] when there is clinical deterioration in spite of maximal medical therapy [Table 5].

These conditions may preclude a transplant operation, and thus it is important that these conditions are looked for and treated before any decision to transplant.[6],[7],[10]

Absolute contraindications

The absolute contraindications which preclude lung transplantation are discussed below [Table 7]. Every effort must be taken to ensure that these absolute contraindications are ruled out prior to listing for lung transplantation.

Malignancy: Active current malignancy is an absolute contraindication. In patients with treated malignancies in the past, the treatment must be deemed to have been curative with a disease-free period of 5 years, though in some malignancies a 2-year disease period is adequate.

Vasculitis screen in patients with suspicion of autoimmune disease or connective tissue disease.

Miscellaneous tests

Blood group – checked twice

Human leukocyte antigen tissue typing

Panel reactive antibody (PRA) screen

Pap smear and mammograms in all female patients every year

Urine analysis, 24-h creatinine clearance

Duplex scan to rule out deep vein thrombosis

Arterial Doppler of the lower limbs in case of suspicion of peripheral vascular disease

Carotid Doppler in patients with suspected vascular disease

Bone densitometry for patients with a history of steroid therapy

Dental clearance

ENT clearance, especially in patients with cystic fibrosis

Nephrology clearance

Evaluation by psychiatrist and social worker.

Donor aspects

Donor selection is crucial, and it is pertinent to note that, among the donor pool only about 17%–20% of the lungs are usable as opposed to much higher rates of usable organs such as kidney, liver, and heart. The ideal donor should have characteristics as listed below [Table 9].

Normal bronchoscopy with minimal or no secretions and no organisms on Gram stain from bronchial lavage

No evidence of aspiration or sepsis

No prior thoracic surgery on the side of harvest.

Transplant decision

This section discusses the decision-making process involved in recommending lung transplant to patients.[5]

Whether transplant is appropriate?

The following three questions need to be considered by the physician/transplant team and only if the answer to each of these questions is “yes,” should a transplant be recommended.

Q.1. Has the disease reached end stage? (Disease point of view)

Q.2. Can the patient tolerate the operation? (Patient point of view)

Q.3. Have all contraindications been ruled out?

Disease point of view

It is crucial that all nontransplant treatment options are tried/considered and found to be futile before decision to transplant.

Patient point of view

The comprehensive assessment by the multidisciplinary team of specialists is important in evaluating each organ system and more importantly in ensuring that there are no absolute contraindications for transplant.

Timing of transplant

The correct timing of transplant operation is a crucial factor which has a significant impact on outcomes.

Transplant window

It is the ideal time period to consider the operation, wherein the lung has reached end stage, but all the other organ systems are well preserved. Such patients do well.

Too well for transplant

Considering transplant in a patient early on in the disease process, that is, before end-stage disease is hazardous. This is because the risks to the patient from the transplant operation would be higher than the risk to the patient from the lung disease.

Too sick for transplant

On the other hand, considering transplant in a patient who has advanced disease with multiorgan failure is inappropriate. This is because the outcomes in the subgroup are often fatal. Furthermore, donor organs are a scarce resource and should be used appropriately.

Decision-making process

Two main risk assessment processes help in decision to register a patient for transplant.

Risk–benefit analysis of transplant operation

If the anticipated are much higher than the possible risks, decision to consider transplant is made. Conversely, if the risks are prohibitive in the face of very little benefit, the patient is strongly dissuaded from having a transplant.

Risks with transplant versus risks without transplant

This is another important consideration which helps in decision-making. If the risks from the disease, without transplant, is much higher than the risks involved in transplant operation, decision to consider transplant is made.

Bridging to lung transplant

When patients, who are on the waitlist for transplant, suddenly deteriorate resulting in MV or institution of extracorporeal membrane oxygenation (ECMO), they may be considered for lung transplant.

Thus, MV and ECMO may be used to “bridge”-selected patients to successful lung transplant.[11],[12],[13],[14],[15],[16] Among our lung transplant patients, we have bridged one patient from ECMO and one patient from MV. The outcome of lung transplant in patients who are bridged from MV or ECMO are acceptable, provided they are stable on MV or ECMO, before transplant.

Situations specific to the India

Late presentation of patients

We have observed quite uniformly that our patients, unlike in the West, present very late in the course of the disease.[5],[17] This is attributable to two factors – Patient factors and physician factors.

Patient factors

By and large Indian patients often dread surgery and end up putting off their decision, until it is too late. In some instances, religious beliefs regarding organ transplantation may deter acceptance to transplant operation even when they are “fit” for a transplant. The inevitable clinical deterioration “forces” them to agree eventually, by which time they are bed bound with muscle wasting and result in stormy postoperative courses and lesser surgical outcomes.

Physician factors

Initial reluctance of physicians to refer patients for transplant may be due to decreased awareness of availability of such a treatment option in India and the suboptimal surgical outcomes in patients who presented late. Our increasing experience and standardizing protocols with improved results has, to an extent, overcome the reluctance and we now are seeing increasing referrals at appropriate time.

Endemicity of tuberculosis

Tuberculosis (TB) is endemic in India and this impacts on both recipients and donors.[5]

In recipients: Special emphasis is to made during pretransplant workup to rule out TB. We have, on one occasion, done mediastinoscopy under high-risk general anesthesia to sample mediastinal nodes and commenced antituberculous therapy after a positive histology report. It is important to diagnose TB and treat appropriately before listing for transplant, in view of postoperative immunosuppression.

In donors: Subclinical TB needs to be excluded in donors before organ retrieval. While the presence of normal chest X-ray with normal bronchoscopy rules out parenchymal pulmonary TB, mediastinal tuberculous lymphadenopathy is quite prevalent in India may be missed. Perhaps, in our country, computed tomography scan of the chest needs to be considered, wherever feasible, as a part of evaluation of donor mediastinum.

Some characteristics of favorable recipient (for the first case when starting a program) based on Indian experience

Age <60 years

Able to walk with oxygen supplement for at least 250 m with or without rest in 6 min

Patients referred appropriately with no evidence of frailty, myopathy, or muscle weakness.

Recipient with COPD would be an ideal first case from the surgical point of view compared to ILD

Single lung transplant has good early results, but lesser long-term survival

Double lung transplant has a difficult early period, but better long-term survival.

Conclusions

For a successful lung or heart–lung transplant, we need to choose carefully the correct recipient, the correct donor, have the transplant team in place and go ahead and be prepared for all the complication which can occur. This would result in patients surviving more than 1 year and reaching a median survival equal to Western figures of 50% at 5 years.